Relationship of serum and dietary vitamin D with high cardiometabolic risk in Mexican systemic lupus erythematosus patients: A cross-sectional study.

Objetive: Serum and dietary vitamin D could influence clinical disease activity and cardiometabolic outcomes in systemic lupus erythematosus (SLE). This study aimed to assess the relationship of serum and dietary vitamin D with cardiometabolic risk in Mexican SLE patients and healthy subjects (HS).Methods: 224 SLE patients and 201 HS were included in this cross-sectional study. Serum calcidiol was measured using a competitive enzyme-linked immunosorbent assay (ELISA). Vitamin D dietary intake was assessed by collecting three 24h food records. Dietary patterns (DPs) were identified using principal component analysis (PCA). Cardiometabolic status was analyzed through biochemical measurements and cardiometabolic indexes.Results: Calcidiol deficiency (<20 ng/mL) was associated with 1.66-fold higher risk of excess weight by body mass index (BMI) (≥25 kg/m2) (p = .02), 2.25-fold higher risk to low high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) (p < .001), and 1.74-fold higher risk to high triglycerides (TG) ≥150 mg/dL (p = .02). Inadequate vitamin D dietary intake was associated with 1.92-fold higher risk of presenting non-healthy waist circumference (WC) (>80 cm) (p < .01), 2.05-fold higher risk of android waist to hip ratio (WHR ≥85) (p < .01), and 1.72-fold higher risk to excess weight (p = .02). Non-adherence to a DP rich in vitamin D food sources was associated with higher WC, WHR, triglycerides, and lower high-density lipoprotein-cholesterol (HDL-C); furthermore, in HS, non-adherence to the DP rich in vitamin D food sources provided 2.11-fold higher risk to calcidiol deficiency.In Cconclusion: A pattern of Calcidiol deficiency, inadequate vitamin D dietary intake, and non-adherence to a DP rich in vitamin D food sources was related to high cardiometabolic risk in SLE patients and HS.

Nutritional, biochemical, and clinical determinants of hyperuricemia in systemic lupus erythematosus patients: Relationship with clinical and renal disease activity.

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease considered as an independent risk factor for mortality by cardiovascular disease. Currently, uric acid is described as a novel biomarker associated with cardiometabolic risk. However, nutritional and serum determinants that influence hyperuricemia development in autoimmune diseases have not been fully elucidated. This study aimed to assess the nutritional, biochemical, and cardiometabolic determinants of hyperuricemia and its relationship with clinical variables in SLE patients. A cross-sectional study was conducted in 167 SLE patients and 195 control subjects (CS). Nutrient intake, anthropometry, biochemical, and cardiometabolic indexes were evaluated. In SLE patients, adequate protein (OR = 0.4; p = 0.04) and carbohydrate (OR = 0.2; p = 0.01) intakes were associated with a lower risk of hyperuricemia. SLE patients with hyperuricemia presented a higher risk of clinical (OR = 2.2; p = 0.03) and renal activity (OR = 3.4; p < 0.01), as well as triglycerides ≥150 mg/dL (OR = 3.6; p < 0.01), hs-CRP ≥1 mg/L (OR = 3.1; p < 0.01), Kannel score ≥3 (OR = 2.5; p = 0.02), and BMI ≥25 kg/m2 (OR = 2.2; p = 0.02). Oppositely, serum levels of HDL-C ≥40 mg/dL (OR = 0.2; p < 0.01) were associated with a lower risk of hyperuricemia. According to the pharmacotherapy administered, prednisone treatment was associated with a high risk of hyperuricemia (OR = 4.7; p < 0.001). In contrast, the hydroxychloroquine treatment was associated with a lower risk of hyperuricemia (OR = 0.4; p = 0.02). In conclusion, SLE patients with hyperuricemia presented a high risk of clinical and renal activity as well as worse cardiometabolic status. Notably, an adequate intake of protein, carbohydrates, healthy HDL-C serum levels, and hydroxychloroquine treatment could be determinants of lower risk of hyperuricemia.

Assessment of the Relationship between Clinical Variants of Psoriasis and Killer Immunoglobulin-like Receptor (KIR) Genes: A Systematic Review with Meta-analysis.

BACKGROUND: Psoriasis (Ps) is an autoimmune dermatosis. Previous studies have shown an association between KIR genes and susceptibility to some clinical variants of Ps. Therefore, we conducted an exhaustive systematic review with meta-analysis to evaluate the relationship between KIR genes and susceptibility to clinical variants of Ps in the overall population and according to ethnicity. METHODS: According to PRISMA guidelines, we performed a systematic review through PubMed and Web of Science to identify relevant available scientific publications about KIR genes and Ps. The quality of the studies was evaluated using the Newcastle-Ottawa scale. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using random and fixed effect models for the analyzed genes. Heterogeneity was tested using Cochran's Q-Statistic and I2, and the risk of bias was tested using the Begg test and Egger linear regression. RESULTS: A total of 10 case-control studies were included, comprising a variable number of KIR typified genes and psoriasis vulgaris (PsV) as the main clinical variant studied. In the total pooled results, the KIR2DS1 gene (OR = 1.518, p = .010, 95%CI: 1.105 to 2.086) was related to higher susceptibility to PsV, while the KIR2DS4 (OR = 0.563, p = .005, 95%CI: 0.376 to 0.842) and KIR3DL1 (OR = 0.602, p = .040, 95%CI: 0.370 to 0.977) genes were related to protection against PsV. CONCLUSION: This meta-analysis demonstrates that subjects that carry the KIR2DS1 gene could have a potential risk factor for the development of PsV. Conversely, KIR2DS4 and 3DL1 genes appear to confer protection against PsV.

Association of cardiometabolic risk status with clinical activity and damage in systemic lupus erythematosus patients: A cross-sectional study.

Cardiometabolic status is a key factor in mortality by cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). This study evaluated the association of cardiometabolic risk status with clinical activity and damage in SLE patients. A cross-sectional study was conducted in 158 SLE patients and 123 healthy subjects (HS). Anthropometry, glucose, hs-CRP, lipid profile, oxLDL, sCD36, anti-oxLDL antibodies, and cardiometabolic indexes were evaluated. SLE patients had dyslipidemia, higher sCD36, anti-oxLDL antibodies, hs-CRP, and risk (OR > 2) to present Castelli score ≥ 4.5, HDL-C < 40 mg/dL and LDL-C ≥ 100 mg/dL. Disease evolution time was correlated with glucose and BMI, damage with TG, and clinical activity with TG, TG/HDL-C ratio, and Kannel index. Active SLE patients had risk (OR > 2) to present a Castelli score ≥ 4.5, Kannel score ≥ 3, TG/HDL-C ratio ≥ 3 and HDL-C < 40 mg/dL. In conclusion, SLE patients have high cardiometabolic risk to CVD related to disease evolution time, and clinical activity.

Association Study between Psoriatic Arthritis and Killer Immunoglobulin-Like Receptor (KIR) Genes: A Meta-Analysis.

Background: Psoriatic Arthritis (PsA) is a seronegative spondyloarthropathy frequently associated with psoriasis. Studies have shown different members of the KIR (Killer Immunoglobulin-like Receptor) gene family may act as potential susceptibility factors; however, data have been inconsistent or with a reduced sample size. Therefore, the objective of this investigation was to determine associations between KIR genes and PsA susceptibility a meta-analysis approach. Methods: We performed a systemic search on PubMed, Scopus, and Web of Science to identify association studies linking KIR genes with PsA susceptibility. The search cut-off was May 2019. Odds Ratio (OR), 95% Confidence Intervals (95% CI), and forest plots were obtained for each KIR gene. Publication bias was evaluated by Begg and Egger linear regression tests. Results: Five articles were included in this meta-analysis. The KIR2DL2, 2DS1, 2DS2, and 2DS3 genes were positively associated with susceptibility to PsA (OR = 1.269, p = .003; OR = 1.392, p < .001; OR = 1.279, p = .002; and OR = 1.230, p = .038, respectively). In Caucasians, positive association with susceptibility to PsA were maintained by KIR2DL2, 2DS1, and 2DS2 genes (OR = 1.257, p = .005; OR = 1.535, p = .003; and OR = 1.267, p = .004, respectively). Conclusion: These associations suggest that KIR2DL2, 2DS1, 2DS2, and 2DS3 genes are susceptibility factors for PsA.

Interaction between 17ß-estradiol, prolactin and human papillomavirus induce E6/E7 transcript and modulate the expression and localization of hormonal receptors.

BACKGROUND: Cervical cancer (CC) is the second most common cancer in less developed countries and the second leading cause of death by cancer in women worldwide. The 99% of CC patients are infected with the Human Papilloma Virus (HPV), being HPV16 and HPV18 infection the most frequent. Even though HPV is considered to be a necessary factor for the development of CC, it is not enough, as it requires the participation of other factors such as the hormonal ones. Several studies have demonstrated the requirement of estrogen and its receptors (ERα, ERß, and GPER) in the precursor lesions progress towards CC. Also, prolactin (PRL) and its receptor (PRLR) have been associated with CC. The molecular mechanisms underlying the cooperation of these hormones with the viral oncoproteins are not well elucidated. For this reason, this study focused on analyzing the contribution of 17ß-estradiol (E2), PRL, and HPV on the expression and localization of hormone receptors, as well as to evaluate whether these hormones may promote greater expression of HPV oncogenes and contribute to tumor progression. METHODS: qPCR was used to evaluate the effect of E2 and PRL on the expression of E6 and E7 oncoproteins in HeLa and SiHa cervical cancer cells lines. HaCaT cells were transduced with the viral oncogenes E6 and E7 from HPV 16 and 18. ERα, ERß, GPER, and PRLR expression and localization were evaluated by qPCR, Western blot and immunofluorescence. RESULTS: E2 and PRL induce E6/E7 oncogenes expression in HeLa and SiHa cells. E6 and E7 oncogenes of HPV16/18 significantly increased the protein expression of ERα, GPER, and PRLR. ERß was positively regulated only by E6 oncogenes of HPV16/18. Besides, some of these oncogenes modify the location of PRLR toward cytoplasm, and ERα, ERß, and GPER mainly to the nucleus. CONCLUSION: Our studies suggest that the mutual regulation between E2, PRL, and HPV oncogenes could cooperate with the carcinogenesis process in CC.

IL10 haplotypes are associated with diabetic nephropathy susceptibility in patients from western Mexico.

INTRODUCTION: Diabetic Nephropathy (DN) is the main cause of chronic kidney disease (CKD) in diabetic patients. An IL-10 imbalance could be related to renal hypertrophy and trigger to nephropathy. Three promoter polymorphisms (-1082G>A, -819C>T, and -592C>A) at IL10 gene have been associated with changes in the IL-10 expression and DN susceptibility. Therefore, the aim of this study was to analyze this association in Mexican patients with DN. METHODS: We conducted a case-control study on 128 patients with DN and 150 control subjects (CS) from western Mexico. All patients were tested for IL10 polymorphisms by PCR-RFLP. Allele frequencies, genotypes, and haplotypes were compared between groups. The significant haplotypes were correlated with patient clinical features. RESULTS: IL10 gene ATC haplotype (-1082A/-819T/-592C) was found significantly more frequent in DN patients than in CS (P < 0.001; OR = 3.6, 95% CI: 1.7-7.4). Similarly GTA (-1082G/-819T/-592A) haplotype was more frequent in DN patients than CS with significant differences (P < 0.05; OR = 4.02, 95% CI: 1.10-14.78). There were no correlations between IL10 haplotypes and clinical parameters in patients with DN. However, that there is a trend of higher serum urea levels and lower eGFR in ATC haplotype carriers compared to carriers of the other haplotypes (P < 0.05). CONCLUSIONS: These results indicate that IL10 promoter haplotypes ATC and GTA carriers have a higher risk factor to develop DN in the western Mexican population.

KIR2DL2 and KIR2DS2 as genetic markers to the methotrexate response in rheumatoid arthritis patients.

CONTEXT: Disease Modifying Anti-Rheumatic Drugs (DMARDs) are aimed to interfere with rheumatoid arthritis (RA) progression and reduce the joint damage; however, not all patients respond alike. Killer-cell immunoglobulin-like receptors (KIR) and their ligands, human leucocyte antigen class I (HLA-I), have been associated with RA pathology; therefore, KIR and HLA genes may influence the treatment response. MATERIALS AND METHODS: We evaluated the association of KIR genotype and their ligands HLA-C genes with the response to DMARDs in RA patients. We included 69 patients diagnosed with RA and 82 healthy individuals as the reference group. KIR and HLA-C genotyping was performed using SSP-PCR. RA patients were assessed at baseline and under treatment at 6 and 12 months; subsequently classified as responders and non-responders in each time period. We evaluated the association between DMARD response and genes using statistical analysis by using Fisher exact test with Bonferroni correction; results were regarded as statistically significant at p < 0.05. RESULTS: Significant difference was observed in gene frequencies of patients and the reference group, KIR2DL2 was associated with RA (p = 0.031, OR = 2.119). We also observed an association between KIR2DS2 and the response to methotrexate (MTX), moreover, the combination KIR2DL2+/KIR2DS2+ was more frequent in responders to MTX (p = 0.043). DISCUSSION AND CONCLUSIONS: In our results, responders and non-responders to DMARDs showed KIR2DS2 and KIR2DL2 different gene frequencies, therefore, these genes could be used as response predictors to DMARDs treatment. Thus, these genes were also associated with disease severity, as well as the treatment response possibly by the immunoregulatory function of NK cells.

Role and New Insights of Pirfenidone in Fibrotic Diseases.

Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-ß1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases. This review contains current research in which PFD has been used as the treatment of several diseases, and focus mainly in the outcomes related to improve inflammation and fibrogenesis. Therefore, the main goal of this review is to focus on the novel findings of PFD efficacy rather than deepen in the chemical aspects of the molecule.

Association of polymorphisms in the TNFA, TNFRSF1A and TNFRSF1B genes with lepromatous leprosy in Western Mexican patients.

INTRODUCTION: Studies in different populations have shown that single-nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and TNF receptors 1 and 2 (TNFR1 and TNFR2) may be involved in the pathogenesis of lepromatous leprosy (LL). To further explore the results in a Mexican population, we compared the frequencies of the polymorphisms in - 308 G>A TNFA (rs1800629), - 383 A>C TNFRS1A (rs2234649), and + 196 T >G TNFSR1B (rs1061622) genes in LL patients (n = 133) and healthy subjects (n = 198). METHODOLOGY: The genotyping was performed with the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) technique. Statistical analysis was performed using the χ2 test, within the 95% confidence interval. Odds ratios (OR) were calculated and Hardy-Weinberg equilibrium was verified for all control subjects and patients. RESULTS: We found an association between the TNFSR1 -383 A>C genotype and the risk of lepromatous leprosy when leprosy patients were compared to controls (OR = 1.71, CI: 1.08-2.69, p = 0.02). Furthermore, it was also associated with the risk of LL in a dominant model (AC + CC vs AA, OR: 1.65, 95% CI: 1.05-2.057, p = 0.02). Similar genotype and allele frequencies for the SNPs TNFA - 308 G>A and TNFSR2 + 196 T>G were observed between leprosy patients and healthy subjects. CONCLUSIONS: The TNFSR1 -383 A>C could be a potential marker for the identification of high-risk populations. However, additional studies, using larger samples of different ethnic populations, are required.

Nutritional Approaches to Modulate Cardiovascular Disease Risk in Systemic Lupus Erythematosus: A Literature Review.

Systemic lupus erythematosus (SLE) is a chronic pathology characterized by a bimodal mortality pattern attributed to clinical disease activity and cardiovascular disease (CVD). A complex interaction between traditional CVD risk factors such as obesity, dyslipidemia, smoking, insulin resistance, metabolic syndrome, and hypertension, as well as the presence of non-traditional CVD risk factors such as hyperhomocysteinemia, pro-inflammatory cytokines, and C-reactive protein levels, has been suggested as a cause of the high prevalence of CVD in SLE patients. On the other hand, environmental factors, such as nutritional status, could influence the disease's prognosis; several nutrients have immunomodulators, antioxidants, and anti-cardiometabolic risk properties which could reduce SLE severity and organ damage by decreasing the development of traditional and non-traditional CVD risk factors. Therefore, this critical literature review discusses the therapeutic potential of nutritional approaches that could modulate the development of the main comorbidities related to CVD risk in SLE patients.

Association of - 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease where genetic factors have been related to SLE susceptibility and disease severity. CRP polymorphisms have been associated with high C-reactive protein (CRP) serum levels, cardiovascular disease (CVD), and high clinical disease activity in SLE patients; however, the evidence is still inconclusive. OBJECTIVE: This study was aimed to assess the association of the - 717 A > G, - 409 G > A, + 1444 C > T, and + 1846 C > T CRP polymorphisms with genetic susceptibility, clinical disease activity, and CVD risk in Mexican-mestizo SLE patients. METHODS: A comparative cross-sectional study was conducted on 369 unrelated women: 183 with SLE according to the 1997 SLE-ACR criteria and 186 healthy subjects (HS). The clinical disease activity was assessed by the Mex-SLEDAI score; CRP and lipid profile were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. The CRP polymorphisms genotyping was carried out by allelic discrimination. RESULTS: SLE patients with - 717 AA genotype had higher CRP serum levels than SLE carriers of AG and GG genotypes (AA = 5 mg/L vs. AG = 3.2 mg/L vs. GG = 2.4 mg/L; p = 0.01), and the AA genotype was associated with high CVD risk by CRP in SLE patients (OR = 3; CI: 1.2-7.6; p < 0.01). CONCLUSIONS: The - 717 A > G CRP polymorphism is a risk factor for high CRP levels and high CVD risk in Mexican-mestizo SLE patients. Key Points • Cardiovascular disease is one of the major causes of death in SLE patients due to the higher prevalence of traditional and non-traditional cardiovascular risk factors. • C-reactive protein is a liver-derived acute-phase protein suggested as one powerful independent risk predictor factor for cardiovascular disease. • Single nucleotide polymorphisms in CRP have been suggested as genetic susceptibility factors that could modify the SLE pathophysiology outcomes. • Mexican-mestizo SLE patients carrying the -717 A>G CRP AA genotype had 3-fold high cardiovascular disease risk than SLE patients with AG or GG genotypes.

CRP Serum Levels Are Associated with High Cardiometabolic Risk and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Systemic lupus erythematosus (SLE) patients have a higher frequency of cardiovascular risk factors such as high C-reactive protein (CRP) levels than the general population. CRP is considered a cardiovascular disease marker that could be related to SLE clinical disease activity. This study aimed to assess the association between CRP with cardiometabolic risk and clinical disease activity in SLE patients. A comparative cross-sectional study was conducted in 176 female SLE patients and 175 control subjects (CS) with median ages of 38 and 33 years, respectively; SLE patients were classified by the 1997 SLE-ACR criteria, and the clinical disease activity by the Mexican-SLEDAI (Mex-SLEDAI). CRP and lipid profile (triglycerides, cholesterol, HDL-C, and LDL-C) were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. SLE patients had higher CRP levels than CS (SLE: 5 mg/L vs. CS = 1.1 mg/L; p < 0.001). In SLE patients, CRP levels ≥ 3 mg/L were associated with a higher risk of cardiometabolic risk status assessed by LAP index (OR = 3.01; IC: 1.04−8.7; p = 0.04), triglycerides/HDL-C index (OR = 5.2; IC: 2.1−12.8; p < 0.001), Kannel index (OR = 3.1; IC: 1.1−8.1; p = 0.03), Castelli index (OR = 6.6; IC: 2.5−17.8; p < 0.001), and high clinical disease activity (OR = 2.5: IC: 1.03−6.2; p = 0.04; and ß coefficient = 5.8; IC: 2.5−9.4; R2 = 0.15; p = 0.001). In conclusion, high CRP levels were associated with high cardiometabolic risk and clinical disease activity in SLE patients.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Diversity of KIR/HLA Genotypes and Their Association with Psoriasis Vulgaris in the Western Mexican Population.

NK and some T cell functions are regulated by the interaction between KIR and HLA molecules. Several studies have shown an association between activating KIR genes and the development of autoimmune diseases, including psoriasis vulgaris (PsV). Our objective was to determine the association between KIR/HLA genes and genotypes with PsV in the Western mestizo Mexican population. One hundred subjects diagnosed with PsV (SP) and 108 healthy subjects (HS) were genotyped for 14 KIR genes, HLA-Bw4, HLA-C1, and HLA-C2 by PCR-single specific primer (SSP). Positive associations of the KIR3DS1 gene (odds ratio (OR) 1.959, p = 0.021), G11 genotype (OR 19.940, p = 0.008), and KIR3DS1/HLA-ABw4 (OR 2.265, p = 0.009) were found with susceptibility to PsV. In contrast, the G1 genotype (OR 0.448, p = 0.031) and KIR3DL1/HLA-Bw4Ile80 (OR 0.522, p = 0.022) were negatively associated with susceptibility to this disease. These results suggest an implication of the KIR3DS1/HLA-ABw4 genotype in PsV pathology.

Relationship of Excess Weight with Clinical Activity and Dietary Intake Deficiencies in Systemic Lupus Erythematosus Patients.

Obesity and nutrients intake deficiencies may contribute to the clinical manifestations and inflammatory processes in systemic lupus erythematosus (SLE). The aim of this study was to assess the relationship between nutritional status and dietary intake with clinical variables in Mexican-mestizo SLE patients. A cross-sectional study was conducted in 130 female SLE patients, classified by the 1997 SLE American College of Rheumatology (ACR) criteria; the clinical activity was evaluated by the Mexican-Systemic Lupus Erythematosus-Disease Activity Index (Mex-SLEDAI); body mass index (BMI) by the World Health Organization (WHO) criteria; the energy calculation and nutritional intake were performed by Nutritionist Pro Diet software. SLE patients with excess weight (BMI > 25 kg/m2) showed a higher score of clinical activity (Mex-SLEDAI = 2; p = 0.003), higher clinical activity prevalence (40.9%; p = 0.039) and a significant association for high clinical activity (odds ratio (OR) = 2.52; 95% confidence interval (CI) = 1.08-5.9; p = 0.033), in comparison with patients without excess weight (BMI < 25 kg/m2). In particular, the excess weight increased the Mex-SLEDAI score (ß coefficient = 1.82; R2 = 0.05; p = 0.005). Also, the SLE patients presented a high prevalence (%) of deficient consumption (cut-off point: <67% of dietary adequacy) of vitamin E (100%), iodine (96%), omega 3 (93.44%), biotin (78%), vitamin K (73.33%), iron (67%), vitamin D (63.3%), potassium (59%), folic acid (56.67%), pantothenic acid (43.3%), vitamin A (41.67%) and zinc (32%). In conclusion, in SLE patients the excess weight was associated with increased clinical activity and to the presence of deficiencies in some essential nutrients ingested.

KIR/HLA Gene Profile Implication in Systemic Sclerosis Patients from Mexico.

INTRODUCTION: Systemic Sclerosis (SSc) is an autoimmune, inflammatory, and multisystemic disease characterized by the presence of autoantibodies and fibrosis. The pathogenesis involves the interaction between immune system cells such as macrophages, NK cells, T cells, and B cells. Killer-cell Immunoglobulin-like Receptors (KIR) are expressed in NK cells and some T cell subsets that recognize HLA class I molecules as ligands and are involved in regulating the activation and inhibition of these cells. The KIR family consists of 14 genes and two pseudogenes; according to the gene content, the genotype could be AA and Bx. The aim of this study was to evaluate the association between KIR/HLA genes and genotypes with SSc and the clinical characteristics. METHODS: We included 50 SSc patients and 90 Control Subjects (CS). Genotyping of KIR, HLA-C, -Bw4, and -A ∗ 03/ ∗ 11 was made by SSP-PCR. RESULTS: In SSc patients, a higher frequency of KIR2DL2 (p = 0.0007, p' = 0.011), KIR2DS4del (p = 0.001, p' = 0.021), and HLA-C2 (p = 0.02, p' = 0.09) was found. This is the first study to evaluate the frequency of HLA-A ∗ 03/ ∗ 11 in SSc patients, of which a low frequency was found in both groups. Compound genotypes KIR2DL2+/HLA-C1+ or KIR2DL2+/HLA-C2+ have a higher frequency in SSc patients. The Bx genotype was the most frequent and was associated with risk to SSc (p = 0.007, OR = 3.1, 95% CI = 1.4-7.9, p' = 0.014). The genotypes with a higher iKIR number than aKIR (iKIR > aKIR) were found in all individuals; genotypes with 7-8 iKIR genes were increased in SSc patients. We do not find an association between the KIR genes with the clinical characteristics. CONCLUSION: The results suggest that KIR2DL2 and 2DS4del could have a risk role in the development of SSc, but not with clinical manifestations.

GPER Overexpression in Cervical Cancer Versus Premalignant Lesions: Its Activation Induces Different Forms of Cell Death.

BACKGROUND: The effect of estrogen has been traditionally studied through the modulation of its alpha and beta nuclear receptors; however, the G Protein-Coupled Estrogen Receptor (GPER) has been recently involved in the pathology of numerous tumors. Although the study of GPER in cervical cancer has begun, its contribution still remains to be completely evaluated. OBJECTIVE: The purpose of this work was to determine the expression of this receptor in different degrees of cervical lesions and whether the stimulation with its specific agonist (G-1) modulated mechanisms of cell survival or cell death in cervical cancer cells. METHODS: Sections of 44 formalin-fixed paraffin-embedded blocks from patients were analyzed by automated immunohistochemistry. After the stimulation with G-1, proliferation was evaluated by the xCELLigence technology, the integrity of the mitochondrial membrane permeability by MitoCaptureTM fluorescence staining, apoptosis by flow cytometry, and senescence by the senescence-associated ß-galactosidase kit. RESULTS: GPER was widely expressed in cervical cancer but not in its precursor lesions. The staining was predominantly cytoplasmic, although it was also important in the nucleus of the epithelial cells. G-1 inhibited proliferation, decreased the mitochondrial permeability, and increased the percentage of apoptosis in SiHa, HeLa, and C-33A. Only in C-33A, an increase of the cells in necrosis was observed, whereas SiHa was the only cell line in which senescence was evidenced. CONCLUSION: GPER is a receptor associated with cervical cancer that inhibits the growth and induces different mechanisms of death in cells derived from uterine cervical cancer. It suggests that GPER can be considered a pharmacological target that prevents the development of cervical carcinogenesis.

The 3'UTR 1188 A/C polymorphism in the interleukin-12p40 gene (IL-12B) is associated with lepromatous leprosy in the west of Mexico.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. IL-12 participates in the immune response against M. leprae by regulating T cell differentiation into the Th1-type response. Several single nucleotide polymorphisms have been identified in the IL-12 gene such as 3'UTR 1188 A/C polymorphism, which is associated with different diseases. However, the relationship of this polymorphism with the immune response in leprosy has not been explored. In this case-control study, we evaluated 44 patients with lepromatous leprosy (LL) and 51 healthy subjects (HS). We aimed to determine the relationship between 3'UTR 1188 A/C polymorphism of IL-12 p40, mRNA expression, and soluble IL-12 concentration in LL patients and HS. Genotype frequencies were 41% A/A, 36% A/C, and 23% C/C in LL patients, and 47% A/A, 49% A/C, and 4% C/C in HS (p<0.05). LL patients had a lower mRNA expression of IL-12 p40 gene, whereas HS had a higher expression level. Soluble IL-12 p40 concentration was higher in LL patients than in HS (p<0.05). IL-12 p70 concentration did not differ between groups, and IL-12 p40 concentration was not significantly correlated with mRNA expression in either group. These data suggest that IL-12 p40 3'UTR 1188 A/C polymorphism is associated with greater susceptibility to lepromatous leprosy in patients from western Mexico, independently of IL-12 p40 and p70 expression levels.

Recovery of IFN-gamma levels in PBMCs from lepromatous leprosy patients through the synergistic actions of the cytokines IL-12 and IL-18.

The shift to the production of a Th1 cytokine profile during an intracellular infection has been shown to depend on antigen presenting cells-derived IL-12 and T-cell-derived IFN-gamma production. IL-18 facilitates Th1 priming in synergy with IL-12 through the stimulation of IFN-gamma production by T cells, B cells, NK cells, macrophages and DCs. A low level of IFN-gamma production in PBMC cultures from lepromatous leprosy patients (LL) has been previously reported by several groups. We evaluated the synthesis of this cytokine after exogenous addition of recombinant IL-12 and IL-18 (IL12/IL18) in order to induce recovery of the IFN-gamma levels with Mycobacterium leprae antigenic stimulation. The aim of this study was to investigate if exogenous addition of IL12/IL18 to PBMC cell cultures in the presence of M. leprae antigens could induce recovery of IFN-gamma levels. We found that IFN-gamma levels in PBMCs cultured from LL patients were reestablished after exogenous addition of exogenous IL12/IL18 and we also observed a diminished IL-18R expression. Although the molecular mechanisms of IL12/IL18 synergy have not been clearly elucidated, we assume that recombinant cytokines can activate several transcription factors that induce IFN-gamma synthesis.